Association and interaction of the IL4R, IL4, and IL13 loci with type 1 diabetes among Filipinos
Association and interaction of the IL4R, IL4, and IL13 loci with type 1 diabetes among Filipinos
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DOI：
10.1086/375655
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发表时间：
2003-06-01
影响因子：
9.8
通讯作者：
Erlich, HA
中科院分区：
文献类型：
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作者：
Bugawan, TL;Mirel, DB;Erlich, HA
在寻找与 1 型糖尿病 (TED) 相关的基因时，除了人类白细胞抗原位点上已确定的风险等位基因之外，我们还研究了 90 名菲律宾 T1D 患者和 94 名对照样本中涉及 IL4/IL13 通路的基因多态性的关联和相互作用。检查了 10 个单核苷酸多态性 (SNP) 的关联、连锁不平衡和相互作用，其中包括 16p11 染色体上 IL4R 基因座中的 2 个启动子 SNP、5q31 染色体上 IL4 基因座中的 1 个启动子 SNP、以及 5q31 染色体上 IL13 基因座中的 4 个 SNP（包括 2 个启动子 SNP）。我们发现IL4R（OR 0.10；95% CI 0-0.5；P = .001）和五个连锁的IL4和IL13 SNP（OR 3.47；P = .004) 与 T1D 易感性密切相关。由于 IL4 和 IL13 均充当部分由 IL4R α 链组成的受体的配体，因此我们寻找染色体 16p11 上的 IL4R 基因座的多态性与染色体 5q31 上的 IL4 和 IL13 基因座的 5 个 SNP 之间的潜在上位性，并通过使用逻辑回归模型发现显着的基因-基因相互作用（P = .045，通过排列校正多重比较）分析）。我们的数据表明，T1D 风险部分取决于 IL4R 位点内的多态性（包括启动子和编码序列变异）以及 IL4R 以及 IL4 和 IL13 位点基因型的特定组合。
In the search for genes involved in type 1 diabetes (TED), other than the well-established risk alleles at the human leukocyte antigen loci, we have investigated the association and interaction of polymorphisms in genes involved in the IL4/IL13 pathway in a sample of 90 Filipino patients with T1D and 94 controls. Ten single-nucleotide polymorphisms (SNPs), including two promoter SNPs in the IL4R locus on chromosome 16p11, one promoter SNP in the IL4 locus on chromosome 5q31, and four SNPs-including two promoter SNPs-in the IL13 locus on chromosome 5q31 were examined for association, linkage disequilibrium, and interaction. We found that both individual SNPs (IL4R L389L; odds ratio [OR] 0.34; 95% confidence interval [CI] 0.17-0.67; P = .001) and specific haplotypes both in IL4R (OR 0.10; 95% CI 0-0.5; P = .001) and for the five linked IL4 and IL13 SNPs (OR 3.47; P = .004) were strongly associated with susceptibility to T1D. Since IL4 and IL13 both serve as ligands for a receptor composed, in part, of the IL4R alpha chain, we looked for potential epistasis between polymorphisms in the IL4R locus on chromosome 16p11 and the five SNPs in the IL4 and IL13 loci on chromosome 5q31 and found, through use of a logistic-regression model, significant gene-gene interactions (P = .045, corrected for multiple comparisons by permutation analysis). Our data suggest that the risk for T1D is determined, in part, by polymorphisms within the IL4R locus, including promoter and coding-sequence variants, and by specific combinations of genotypes at the IL4R and the IL4 and IL13 loci.